Surf Wiki
Save to docs
science/chemistry

From Surf Wiki (app.surf) — the open knowledge base

S-Nitrosylation

Biochemical reaction; attachment of –NO to cysteine in a protein

Summary

Biochemical reaction; attachment of –NO to cysteine in a protein

In biochemistry, S-nitrosylation is the covalent attachment of a nitric oxide group () to a thiol on a cysteine within a protein to form an S-nitrosothiol (SNO). S-Nitrosylation has diverse regulatory roles in bacteria, yeast and plants, and in all cells in mammals. It thus operates as a fundamental mechanism for cellular signaling across phylogeny and accounts for the large part of NO bioactivity.

S-Nitrosylation is precisely targeted, reversible, spatiotemporally restricted and necessary for a wide range of cellular responses, including the prototypic example of red blood cell mediated autoregulation of blood flow that is essential for vertebrate life. Although originally thought to involve multiple chemical routes in vivo, accumulating evidence suggests that S-nitrosylation depends on enzymatic activity, entailing three classes of enzymes (S-nitrosylases) that operate in concert to conjugate NO to proteins, drawing analogy to ubiquitinylation. Beside enzymatic activity, hydrophobicity and low pka values also play a key role in regulating the process.S-Nitrosylation was first described by Stamler et al. and proposed as a general mechanism for control of protein function, including examples of both active and allosteric regulation of proteins by endogenous and exogenous sources of NO. The redox-based chemical mechanisms for S-nitrosylation in biological systems were also described concomitantly. Important examples of proteins whose activities were subsequently shown to be regulated by S-nitrosylation include the NMDA-type glutamate receptor in the brain. Aberrant S-nitrosylation following stimulation of the NMDA receptor would come to serve as a prototypic example of the involvement of S-nitrosylation in disease. S-Nitrosylation similarly contributes to physiology and dysfunction of cardiac, airway and skeletal muscle and the immune system, reflecting wide-ranging functions in cells and tissues. It is estimated that ~70% of the proteome is subject to S-nitrosylation and the majority of those sites are conserved. S-Nitrosylation is also known to show up in mediating pathogenicity in Parkinson's disease systems. S-Nitrosylation is thus established as ubiquitous in biology, having been demonstrated to occur in all phylogenetic kingdoms and has been described as the prototypic redox-based signalling mechanism,

Denitrosylation

The reverse of S-nitrosylation is denitrosylation, principally an enzymically controlled process. Multiple enzymes have been described to date, which fall into two main classes mediating denitrosylation of protein and low molecular weight SNOs, respectively. S-Nitrosoglutathione reductase (GSNOR) is exemplary of the low molecular weight class; it accelerates the decomposition of S-nitrosoglutathione (GSNO) and of SNO-proteins in equilibrium with GSNO. The enzyme is highly conserved from bacteria to humans. Thioredoxin (Trx)-related proteins, including Trx1 and 2 in mammals, catalyze the direct denitrosylation of S-nitrosoproteins (in addition to their role in transnitrosylation). Aberrant S-nitrosylation (and denitrosylation) has been implicated in multiple diseases, including heart disease, cancer and asthma as well as neurological disorders, including stroke, chronic degenerative diseases (e.g., Parkinson's and Alzheimer's disease) and amyotrophic lateral sclerosis (ALS).

Transnitrosylation

Another interesting aspect of S-nitrosylation includes the protein protein transnitrosylation, which is the transfer of an NO moiety from a SNO to the free thiols in another protein. Thioredoxin (Txn), a protein disulfide oxidoreductase for the cytosol and caspase 3 are a good example where transnitrosylation is significant in regulating cell death. Another example include, the structural changes in mammalian Hb to SNO-Hb under oxygen depleted conditions helps it to bind to AE1 (Anion Exchange, a membrane protein) and in turn gets transnitrosylated the later. Cdk5 (a neuronal-specific kinase) is known get nitrosylated at cysteine 83 and 157 in different neurodegenerative diseases like AD. This SNO-Cdk5 in turn is nitrosylated Drp1, the nitrosylated form of which can be considered as a therapeutic target.

References

References

  1. (March 2012). "Enzymatic mechanisms regulating protein S-nitrosylation: implications in health and disease". Journal of Molecular Medicine.
  2. (September 2001). "Cysteine-3635 is responsible for skeletal muscle ryanodine receptor modulation by NO". Proceedings of the National Academy of Sciences of the United States of America.
  3. (September 1995). "S-nitrosoglutathione reversibly inhibits GAPDH by S-nitrosylation". The American Journal of Physiology.
  4. (October 2000). "Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON". Neuron.
  5. (December 2006). "Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking". Proceedings of the National Academy of Sciences of the United States of America.
  6. (February 2005). "Protein S-nitrosylation: purview and parameters". Nature Reviews. Molecular Cell Biology.
  7. (May 2015). "Hemoglobin βCys93 is essential for cardiovascular function and integrated response to hypoxia". Proceedings of the National Academy of Sciences of the United States of America.
  8. (February 2018). "A Multiplex Enzymatic Machinery for Cellular Protein S-nitrosylation". Molecular Cell.
  9. (January 1992). "S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds". Proceedings of the National Academy of Sciences of the United States of America.
  10. (September 1992). "S-nitrosylation of tissue-type plasminogen activator confers vasodilatory and antiplatelet properties on the enzyme". Proceedings of the National Academy of Sciences of the United States of America.
  11. (1992). "The biology of nitric oxide: proceedings of the 2nd International Meeting on the Biology of Nitric Oxide, London". Portland Press.
  12. (December 1992). "Biochemistry of nitric oxide and its redox-activated forms". Science.
  13. (June 1992). "Effect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex". Neuron.
  14. (August 1993). "A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds". Nature.
  15. (December 2015). "Aberrant protein S-nitrosylation contributes to the pathophysiology of neurodegenerative diseases". Neurobiology of Disease.
  16. (April 2008). "A SNO storm in skeletal muscle". Cell.
  17. (September 2009). "Protein S-nitrosylation in health and disease: a current perspective". Trends in Molecular Medicine.
  18. (April 2016). "Identification of novel S-nitrosation sites in soluble guanylyl cyclase, the nitric oxide receptor". Journal of Proteomics.
  19. (April 2019). "Protein S-Nitrosylation: Determinants of Specificity and Enzymatic Regulation of S-Nitrosothiol-Based Signaling". Antioxidants & Redox Signaling.
  20. (June 2021). "Neurodegeneration: Impact of S-nitrosylated Parkin, DJ-1 and PINK1 on the pathogenesis of Parkinson's disease". Archives of Biochemistry and Biophysics.
  21. (April 2012). "Endogenous protein S-Nitrosylation in E. coli: regulation by OxyR". Science.
  22. (July 2007). "Balancing reactivity against selectivity: the evolution of protein S-nitrosylation as an effector of cell signaling by nitric oxide". Cardiovascular Research.
  23. (March 2001). "A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans". Nature.
  24. (November 2005). "Thioredoxin and lipoic acid catalyze the denitrosation of low molecular weight and protein S-nitrosothiols". Journal of the American Chemical Society.
  25. (July 2007). "Thioredoxin catalyzes the denitrosation of low-molecular mass and protein S-nitrosothiols". Biochemistry.
  26. (May 2008). "Regulated protein denitrosylation by cytosolic and mitochondrial thioredoxins". Science.
  27. (2018). "Nitric Oxide".
  28. (January 2012). "Nitric oxide and cancer: the emerging role of S-nitrosylation". Current Molecular Medicine.
  29. (September 2012). "S-nitrosylation of EGFR and Src activates an oncogenic signaling network in human basal-like breast cancer". Molecular Cancer Research.
  30. (August 2002). "S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death". Science.
  31. (July 2004). "Nitrosative stress linked to sporadic Parkinson's disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activity". Proceedings of the National Academy of Sciences of the United States of America.
  32. (May 2006). "S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration". Nature.
  33. (April 2009). "S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury". Science.
  34. (February 2006). "S-nitrosothiol depletion in amyotrophic lateral sclerosis". Proceedings of the National Academy of Sciences of the United States of America.
  35. (February 2001). "Export by red blood cells of nitric oxide bioactivity". Nature.
  36. (January 2013). "Emerging role of protein-protein transnitrosylation in cell signaling pathways". Antioxidants & Redox Signaling.
Wikipedia Source

This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page.

protein-structure protein-biosynthesis chemical-reactions
Want to explore this topic further?

Ask Mako anything about S-Nitrosylation — get instant answers, deeper analysis, and related topics.

Research with Mako

Free with your Surf account

Content sourced from Wikipedia, available under CC BY-SA 4.0.

This content may have been generated or modified by AI. CloudSurf Software LLC is not responsible for the accuracy, completeness, or reliability of AI-generated content. Always verify important information from primary sources.

Report